Inflammation as a Mechanism of Bipolar Disorder Neuroprogression

Barichello, Tatiana; Giridharan, Vijayasree V.; Bhatti, Gursimrat; Sayana, Pavani; Doifode, Tejaswini; Macêdo, Danielle Silveira; Quevedo, Joao L De

doi:10.1007/7854_2020_173

Cited by 10 publications

(11 citation statements)

References 140 publications

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“…As noted above, lifetime depression was associated with lower FA in the FMIN cluster, suggesting that the cumulative effect of years of BD might cause structural abnormalities in this region and increase the risk for recurrence of future depressive episodes. These findings are in line with the neuroprogression of BD [ 59 , 60 , 61 ]. However, while the anterior portion of the CB was associated with lifetime depression, only the posterior CB was associated with future recurrence of depression.…”

Section: Discussionsupporting

confidence: 87%

“…Our findings revealed that lower fiber collinearity in these tracts could reflect the cumulative effect of years of depressive symptoms. In BD, incidence of mood symptoms has been associated with progressive and cumulative neuronal damage [ 59 , 60 , 61 ]. This process, called neuroprogression, is associated with worsening of BD and progressive clinical deterioration over the years [ 59 , 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…In BD, incidence of mood symptoms has been associated with progressive and cumulative neuronal damage [ 59 , 60 , 61 ]. This process, called neuroprogression, is associated with worsening of BD and progressive clinical deterioration over the years [ 59 , 60 , 61 ]. It is hypothesized that persistence and recurrence of mood episodes could lead to permanent alterations in neuronal circuits through increased oxidative stress and inflammation [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

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White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder

Santos

Bertocci

Bebko

et al. 2022

JCM

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Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder

Santos

Bertocci

Bebko

et al. 2022

JCM

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“…Therefore, the alterations in the brain structures reflected the underlying processes of neurotoxicity and immune activation ( 62 , 63 ). The neuroinflammation existing in BD could facilitate the production of neurotoxic metabolites via KYN pathway, which further contributed to the brain dysfunction and neuropathogenesis in BD.…”

Section: Current Findings Indicating the Kyn Pathway Alterations In Bdmentioning

confidence: 99%

Involvement of Kynurenine Metabolism in Bipolar Disorder: An Updated Review

et al. 2021

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Bipolar disorder (BD) is a severe affective disorder, mainly characterized by alternative depressive and manic or hypomanic episodes, yet the pathogenesis of BD has not been fully elucidated. Recent researches have implicated the altered kynurenine (KYN) metabolism involved in the neurobiology of BD. Excessive activation of the immune system also occurs in patients with BD, which further accelerates the KYN pathway for tryptophan metabolism. Changes of the KYN metabolites have effects on neuronal receptors and are involved in neuroendocrine transmissions. Interactions between KYN metabolism and the immune system may contribute to the neuropathogenesis of BD. Various studies have shown that alterations of the KYN metabolites were associated with mood, psychotic symptoms, and cognitive functions in patients with BD. In this review, we briefly introduce the KYN pathway and describe the immune dysregulation in BD as well as their interactions. We then focus on the research advances on the KYN metabolism in BD, which hold promise for identifying novel treatment targets in patients stricken with this disorder.

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“…The involvement of inflammation in mental illness [ 36 ], including schizophrenia [ 37 – 40 ], bipolar disorder [ 41 ], and suicidal behavior [ 42 – 45 ], has been increasingly recognized. For instance, individuals with schizophrenia have a peripheral blood elevation of interleukin (IL) 6, IL-1β, and transforming growth factor-β1 (TFG-β1) [ 28 ], and, centrally, have molecular and visual markers of microglia activation relative to healthy controls [ 29 ], leading to ongoing vulnerability to immunological challenges and psychological stress.…”

Section: Introductionmentioning

confidence: 99%

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

et al. 2021

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Objective Psychiatric hospitalizations and emergency department (ED) visits are costly, stigmatizing, and often ineffective. Given the immune and kynurenine activation in bipolar disorder (BD) and schizophrenia, as well as the immune-modulatory effects of statins, we aimed to compare the relative risk (RRs) of psychiatric hospitalizations and ED visits between individuals prescribed lipophilic vs. hydrophilic statins vs. no statins. We hypothesized (a) reduced rates of hospitalization and ER utilization with statins versus no statins and (b) differences in outcomes between statins, as lipophilia increases the capability to penetrate the blood–brain barrier with potentially beneficial neuroimmune, antioxidant, neuroprotective, neurotrophic, and endothelial stabilizing effects, and, in contrast, potentially detrimental decreases in brain cholesterol concentrations leading to serotoninergic dysfunction, changes in membrane lipid composition, thus affecting ion channels and receptors. Methods We used VA service utilization data from October 1, 2010 to September 30, 2015. The RRs for psychiatric hospitalization and ED visits, were estimated using robust Poisson regression analyses. The number of individuals analyzed was 683,129. Results Individuals with schizophrenia and BD who received prescriptions for either lipophilic or hydrophilic statins had a lower RR of psychiatric hospitalization or ED visits relative to nonstatin controls. Hydrophilic statins were significantly associated with lower RRs of psychiatric hospitalization but not of ED visits, compared to lipophilic statins. Conclusion The reduction in psychiatric hospitalizations in statin users (vs. nonusers) should be interpreted cautiously, as it carries a high risk of confounding by indication. While the lower RR of psychiatric hospitalizations in hydrophilic statins relative to the lipophilic statins is relatively bias free, the finding bears replication in a specifically designed study. If replicated, important clinical implications for personalizing statin treatment in patients with mental illness, investigating add-on statins for improved therapeutic control, and mechanistic exploration for identifying new treatment targets are natural next steps.

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Inflammation as a Mechanism of Bipolar Disorder Neuroprogression

Cited by 10 publications

References 140 publications

White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder

White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder

Involvement of Kynurenine Metabolism in Bipolar Disorder: An Updated Review

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

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